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Alzheimer' s disease (AD) is a neurodegenerative disease that progresses with age and is clinically characterized by cognitive impairment, memory decline, mental symptoms and behavioral disorders. Oxidative stress emerges when an imbalance exists between the generation of free radicals and the antioxidant capacity to scavenge them in the body, and the resulting oxidative injury is closely related to the occurrence of AD. Oxidative stress leads to the mass production of free radicals, which increases the oxidation of macromolecules of nerve cells, the aggregation of β amyloid (Aβ) and the excessive phosphorylation of tau protein and forms the neurofibrillary tangles, thereby inducing apoptosis of nerve tissue cells. In addition, a large number of free radicals can also cause brain inflammatory response and aggravate nerve tissue injury. This paper mainly reviews the pathogenesis of AD and its relationship with oxidative stress, aiming to provide ideas for clinical research.
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Objective To explore the clinical and neuroimaging features of a frontotemporal dementia with parkinsonism linked to chromosome 17 ( FTDP-17 ) pedigree caused by mutation of microtubule-associated protein tau ( MAPT) gene.Methods The proband and one patient from a FTDP-17 pedigree were assessed through standardized clinical evaluation , neuropsychology assessment , video-electroencephalogrom ,MRI, genetic sequencing , as well as 18 F fludeoxyglucose ( FDG) SPECT for brain metabolism and 11 C 2β-carbomethoxy-3β-( 4-fluoro ) tropane ( CFT ) PET for dopamine transporter ( DAT ) distribution, respectively.Results A FTDP pedigree with 15 patients (6 still alive) was recruited to this study.The proband and one affected patient were genotyped and confirmed as MAPT c .1788T>G mutation. Parkinsonism was the first symptom for both two patients . Personality, speech changes and dementia accompanied with brain atrophy were developed at the later stage in one patient .The 18 F FDG SPECT studies illustrated asymmetric hypometabolism of the temporal , frontal lobes and basal ganglia in two patients . Regarding to the 11 C CFT PET, one affected patient showed asymmetric decreased uptake of tracer in basal ganglia regions.Conclusions FTDP-17 can display a confusingly broad clinical phenotype , with the parkinsonism as the first symptom . Brain glucose metabolism and DAT distribution could be potential biomarkers in early diagnosis of FTDP-17.
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Objective To investigate the different components of Acorus tatarinowii and Polygala tenuifolia(volatile oil, aqueous extract)on the expression of phosphorylated Tau protein at site Ser396 and Tau-5 in the hippocampus of rats with Alzheimer′s disease(AD). Methods Male Sprague Dawley rats were randomly divided into 8 groups:normal control group, model control group,low-,middle-,and high-dose groups of volatile oil of Acorus tatarinowii and Polygala tenuifolia,and low-, middle-,and high-dose groups of aqueous extract of Acorus tatarinowii and Polygala tenuifolia. The subacute aging model was established by intraperitoneal injection of D-galactose( D-gal). Rats were given different components of Acorus tatarinowii and Polygala tenuifolia(crude drug dosage,0.6,1.2,1.8 g·kg-1 )in experimental groups,and 0.9% sodium chloride solution in normal control group and model control group,by gavage for 28 days.The levels of phosphorylated Tau protein at site Ser396 and Tau-5 were detected in hippocampal tissues by Western blotting and immunohistochemistry. Results The levels of phosphorylated Tau protein at site Ser396 were significantly enhanced in the model control group,as compared with those in normal control group (P0.05). Conclusion Acorus tatarinowii and Polygala tenuifolia could promote the dephosphorylation of Ser396 site of Tau protein in the hippocampus of AD rats,with the aqueous extract component having better effects.
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Tau is the most abundant microtubule-associated protein in the brain .If tau protein lost the normal function, the toxic effect should be showed and plays an important role in various central nervous system lesions .Hypoxic-ischemic encephalopathy ( HIE) is an important cause of mortality in the neonatal period and it is mainly characterized by neurological deficits such as cognitive limitations .However , the mechanism still needs further study , and the underlying re-lationship between tau protein and HIE lacks direct evidence .Some recent clinical study reported that tau protein expres-sion elevated in the serum of asphyxia children and had a high correlation with behavior deficient .In this review , we focus on 3 key points to provide new insights to understand the tau protein-related pathogenesis of HIE as followed:(1) tau pro-tein and its phosphorylation change during central nervous system development ;(2) comparison of tau protein expression in developing brain and adult brain under some neurological disorders;(3) potential pathological change of tau in HIE related pathological conditions , such as dysmyelination , inflammation response and glutamate metabolism .
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Objective To explore the reversion of astragaloside and NMDA receptor antagonist against the hyperphosphorylation of protein Tau induced by fetal intrauterine distress in neonatal rats.Methods The analysis of variance of factorial design was setted up two intervention factors which were fetal intrauterine distress (two levels:no disposition;a course of fetal intrauterine distress)and the drugs (three levels:iv Saline;iv astragaloside;iv MK -801).When the neonatal rats grew to 12weeks,the hippocampus was removed from the neonatal rats.Detected the content of glutamate in the hippocampus of rats by high performance liquid chromatography.The expression of protein Tau which includes p -AT8Ser202 and GSK -3β1H8 in the hippocampus of rats were detected by the methods of immunohistochemistry staining.Results Fetal intrauterine distress could significantly up -regulate the content of glutamate,which was not affected by MK -801,in the hippocampus of neonatal rats which was reduces by the astragaloside (P <0.05).And both influences presented subtracting effects (P <0.05).Fetal intrauterine distress and the drugs do not affect the total protein Tau in the hippocampus of rats (P <0.05).Fetal intrauterine distress could up -regulate the hyperphosphorylation of protein Tau in the hippocampus of neonatal rats which could be reduced by astragaloside and MK -801 (P <0.05).And the influences between fetal intrauterine distress and the drugs presented subtracting effects (P <0.05 ).Conclusion Our results indicate that fetal intrauterine distress reduce the hyperphosphorylation of protein Tau in neonatal rats though up -regulating the content of glutamate.GSK-3βis the key protein in this signaling pathway.
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Alzheimer's disease (AD) is the general neurodegenerative disease in the elderly. Alterations of microtubule associated pro-tein tau are closely related to the onset and progression of AD. The role of tau protein in the development of AD has been a focus in the cur-rent study of AD, with an emphasis on the identification of compounds that inhibit tau protein phosphorylation and aggregate, and accelerate tau protein depolymerization. The current research status of tau protein as target of AD preventive and therapeutic drug was also reviewed.
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@#Alzheimer's disease (AD) is the general neurodegenerative disease in the elderly. Alterations of microtubule associated protein tau are closely related to the onset and progression of AD. The role of tau protein in the development of AD has been a focus in the current study of AD, with an emphasis on the identification of compounds that inhibit tau protein phosphorylation and aggregate, and accelerate tau protein depolymerization. The current research status of tau protein as target of AD preventive and therapeutic drug was also reviewed.
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Objective To develop a model that could roundly show the phenotypes of human alzheimer disease (AD), the triple-transgenic rat model harboring APP(Swe), PS1dE9, and TAU transgenes was established in view of the advantage of rat as an important animal model on the research of nerve system .Methods APPswe/PS1dE9/TAU triple transgenic rat AD rats were generated on a SD background by co-injecting rat pronuclei with two human genes driven by the mouse prion promoter:‘Swedish’ mutant human APP (APPsw) and exon 9 mutant human presenilin-1 (PS1dE9) and human microtubule-associated protein tau gene under the control of PDGF promoter .Transgene integration was confirmed by genotyping and expression levels were evaluated by western blot ( WB ) of brain homogenates .The pathological changes were detected by human Abeta, TAU and Phospho-PHF-TAU immunohistochemistry staining (IHC).The behavioral and cognitive changes were evaluated by Morris water maze .Results One transgenic rat lines with high human APP ( Swe ) , PS1dE9, and TAU transgenic expression was selected from three transgenic founders .Compared with the wild type rat , the transgenic rat showed significant learning and memory impairments in the Morris water maze at 6 months of age .The triple transgenic rat manifested hyperphosphorylated tau and obvious aggregation of amyloid -β( Aβ) in the brain cortex and hippocampus.Conclusion APPswe/PS1dE9/TAU triple transgenic rat AD model was established .The triple transgenic AD rat fills a critical need for a next-generation animal model to enable basic and translational AD research .
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Objective To explore the level changes of proteins related to non-demyelinating diseases in the cerebrospinal fluid and serum in patients with relapsing-remitting multiple sclerosis (RRMS) of different clinical stages.Methods Twenty-three patients with RRMS,10 patients with head pain (controls) and 10 healthy volunteers (healthy controls),admitted to our hospital from July 2011 to December 2012,were selected.The cerebrospinal fluid sample and blood serum sample were selected in observation group at admission (acute stage) and follow-up (remission phase),control group (during headache) to measure the levels of protein tau,S 100 and neurofilament (NF).Expanded disability status scale (EDSS) was employed to detect the dysneuria and the relation with the protein levels were analyzed.Results In the cerebrospinal fluid,the protein levels of tau,S100 and NF in the observation group both in acute phase and remission phase were significantly higher than those in the control group and healthy control group (P＜0.05); and the levels of three protein in acute phase was higher than those in remission phase (P＜0.05).In blood serum:the protein levels oftau and NF in the observation group in both acute phase and remission phase showed no obvious differences as compared with those in the control group and healthy control group (P＞0.05),but the level of S100 in observation group in both acute phase and remission phase was obviously higher than the control group and healthy control group (P＜0.05); and the levels of three protein in acute phase was higher than those in remission phase (P＜0.05).The EDSS scores of observation group in acute phase and remission phase were (6.0 ±1.5) and (2.8 ±0.7) points,respectively; the protein levels of tau,S 100 and NF in mild EDSS scores patients were significantly lower than those of patients of medium and heavy EDSS scores in acute phase; the protein levels of tau,S100,NF in medium EDSS scores patients had no obvious differences as compared with those of heavy ones (P＞0.05).In remission phase,the tau,S100,NF protein levels of mild EDSS acores patients showed no obvious differences as compared with those of medium ones.Conclusion The protein levels of tau,S100 and NF increase in acute phase of patients with RRMS,which correlates with the EDSS scores,and those decrease in remission phase then,indicating that tau,S100 and NF might be the specific protein markers of non-demyelinating diseases.